The objective of this project is to increase understanding of the role of phospholipid metabolism during inflammatory and immune responses. During the past year a study determining the effects of microtubule-active agents on phosphatidylinositol turnover induced by concanavalin A in lymphocytes has been completed. In this study both the incorporation of 32P into all phospholipids and the incorporation of 3H-inositol into phosphatidylinositol (PI) were followed. Vinblastine, an agent known to bind to tubulin and thereby disrupt microtubules, was found to inhibit the Con A induced incorporation of both isotopes into PI and also inhibit the incorporation of 32P into PC. At the same time, vinblastine increased the incorporation of both isotopes in the absence of Con A. Heavy water (D2O) is known to increase the occurrence of microtubules. Surprisingly it had effects very similar to vinblastine. It inhibited Con A induced phospholipid metabolism while enhancing incorporation in the absence of Con A. These results suggest an action by vinblastine and D2O on phospholipid metabolism either in place of or in addition to the known effect of these agents on microtubules.